The overall goal of this study is to investigate structure-function relationships of cell-surface membrane components expressed on cytotoxic T lymphocytes (CTL). This objective is being approached through the use of a novel immunization procedure based on "tolerization" of the host's response against a given set of unwanted cell-bound antigens represented on noncytotoxic T helper clones. During the period of unresponsiveness, treated animals are then immunized against a functionally distinct clone of CTL in hopes of directing an immune response against killing-relevant membrane structures. Significant progress has been made in optimizing the conditions for cyclophosphamide-induced "tolerance" in both mice and rats. Evidence was obtained that the cellular compartment affected by this treatment was indeed that of the B lymphocyte rather than through the induction of suppressor systems. Using these established conditions for abrogating unwanted B-cell reponses, we have succeeded in making several interesting monoclonal antibodies against clones of alloreactive T cells.